The bed nucleus of the stria terminalis (BNST) is a region of the extended amygdala in which multiple neuropeptide systems, including oxytocin and corticotropin releasing factor (CRF), have the potential to interact and regulate anxiety-like behaviors. Although oxytocin is known to be released into the BNST during times of stress, it is unknown what effect oxytocin release in the BNST has on anxiety behavior. We have demonstrated the presence of oxytocin receptors on discrete populations of BNST neurons that contain other neuropeptides involved in modulating the stress response, such as CRF, enkephalin (Enk), and neuropeptide Y (NPY). CRF is the prototypical stress hormone, which is thought to trigger the behavioral stress response, whereas NPY and Enk are thought of as factors that act to attenuate the stress response. Hence, oxytocin release in the BNST may affect two diametrically opposed components of the stress response. However, the electrophysiological response of these neuronal populations to oxytocin receptor activation has yet to be explored. The central hypothesis of this proposal is that oxytocin differentially regulats the activity of oxytocin responsive neurons in the BNST to decrease anxiety behavior. This project will first aim to determine the effect of oxytocin in the BNST on anxiety-like behavior in mice. Using site specific injection of an oxytocin agonist and antagonist into the BNST, anxiety behavior will be tested with the elevated plus maze and open field paradigms. Additionally, this project will aim to characterize the genotypic, electrophysiological, and oxytocin- response profile of cells expressing the oxytocin receptor in the BNST. Using two novel transgenic mice driving fluorescent protein expression in either CRF neurons or oxytocin receptor-expressing neurons to facilitate visually guided patch, I will perform patch-clamp electrophysiology and single cell reverse transcriptase PCR (scRT-PCR) to characterize these cells and their response to oxytocin. The combination of behavioral, electrophysiological, and molecular approaches will help us move away from considering the BNST as a homogenous group of neurons, but rather a complex structure with multiple neurotransmitter systems that interact to affect the physiological and behavioral output of the nucleus. Elucidating oxytocin's interactions with other neurotransmitter systems in the BNST could lead to a greater understanding of the etiology of and therapeutic strategies for anxiety disorders.

Public Health Relevance

This project will be crucial in determining how oxytocin treatment could affect the neural circuitry of anxiety-like behavior, and will inform future studie on the use of oxytocin or molecules that manipulate oxytocin as treatment for anxiety disorders. The proposed research is expected to contribute to an understanding of how oxytocin acts on different cell types in the bed nucleus of the stria terminalis (BNST) and how this affects anxiety behaviors.